Despite significant advances in diagnosis and therapy, cardiovascular events remain a major common cause of morbidity and mortality. Thus, prevention of cardiovascular events such as myocardial infarction and stroke is an area of major public health importance.
Screening tests for several risk factors for future cardiovascular events have been described and are in clinical use in the detection of human subjects at high risk. Such screening tests include, for example, cholesterol, low density lipoprotein cholesterol (LDLC), and, more recently, C-reactive protein (CRP).
Human subjects with risk factors for cardiovascular event(s) are prescribed therapies to reduce the risk of a future cardiovascular event. For example, human subjects with abnormally high cholesterol and/or LDLC levels are frequently prescribed a class of drugs called statins to reduce cholesterol levels to reduce the risk of a future cardiovascular event. However, the beneficial effects of such agents in human subjects vary in magnitude among different human subjects. The cause for this variation in response to therapy among human subjects is not clearly known yet.
Elevated levels of CRP had been described among human subjects with acute ischemia or myocardial infarction, and predict episodes of recurrent ischemia among those hospitalized with unstable angina. Elevated levels of CRP also have been associated with risk of myocardial infarction among human subjects, such as those with symptomatic angina pectoris. Subsequently, elevated levels of CRP were determined to be predictive of future cardiovascular events in human subjects otherwise healthy. The predictive capacity of CRP was also determined to be independent of the predictive capacity of lipids such as cholesterol. Notwithstanding that CRP and lipids are independent predictors, it has been discovered that lipid-lowering statin therapy of human subjects lowers not only cholesterol but also lowers the level of CRP.
Whether lowering CRP to a target level, however, leads to a lowering of the risk of future cardiovascular event is unknown. In other words, it is unknown whether a statin therapy would achieve its full benefit if it only lowers cholesterol levels or whether a full benefit is only achieved by lowering CRP levels as well. A recent study by Kent et al. (Am J Cardiol 2003; 92:1227-1230) showed that the likelihood of carotid intima-media thickness (CMIT) regression (a measure of vascular atherosclerotic disease) in human subjects was unrelated to levels of CRP when the LDLC levels was below 70 mg/dL or above 100 mg/dL. Kent et al. found no relation between the change in CMIT and either the baseline CRP or the change in CRP. To date, there are no studies that teach or suggest the use of CRP levels to guide therapy.
At this time only a few tests are available to determine whether certain therapies with cardiovascular agents, such as statins, are effective or are expected to be more or less beneficial in reducing future cardiovascular event(s). Thus, there is a need for improved tests and approaches to evaluate therapy in human subjects.